帕博丽珠单抗治疗晚期黑色素瘤的不良事件及相关性分析

杨晓玲; 斯 璐; 毛丽丽; 崔传亮; 迟志宏; 盛锡楠

doi:10.19401/j.cnki.1007-3639.2020.05.007

您当前的位置：

首页 >

文章列表页 >

帕博丽珠单抗治疗晚期黑色素瘤的不良事件及相关性分析

论著 | 更新时间：2026-01-27

- 帕博丽珠单抗治疗晚期黑色素瘤的不良事件及相关性分析
- Adverse events of pembrolizumab in patients with advanced melanoma and correlation analysis
- 中国癌症杂志 2020年30卷第5期页码：362-368
- 作者机构：
  
  北京大学肿瘤医院暨北京市肿瘤防治研究所肾癌黑色素瘤科，恶性肿瘤发病机制及转化研究教育部重点实验室,北京,100142
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2020.05.007
  中图分类号： R739.5
- 网络出版：2020-06-08，
  
  纸质出版：2020-06-08
- 稿件说明：
移动端阅览
杨晓玲, 斯璐, 毛丽丽, 王轩, 崔传亮, 迟志宏, 盛锡楠, 郭军. 帕博丽珠单抗治疗晚期黑色素瘤的不良事件及相关性分析[J]. 中国癌症杂志, 2020, 30(5): 362-368.

杨晓玲, 斯璐, 毛丽丽, et al. Adverse events of pembrolizumab in patients with advanced melanoma and correlation analysis[J]. China Oncology, 2020, 30(5): 362-368.
杨晓玲, 斯璐, 毛丽丽, 王轩, 崔传亮, 迟志宏, 盛锡楠, 郭军. 帕博丽珠单抗治疗晚期黑色素瘤的不良事件及相关性分析[J]. 中国癌症杂志, 2020, 30(5): 362-368. DOI： 10.19401/j.cnki.1007-3639.2020.05.007.

杨晓玲, 斯璐, 毛丽丽, et al. Adverse events of pembrolizumab in patients with advanced melanoma and correlation analysis[J]. China Oncology, 2020, 30(5): 362-368. DOI： 10.19401/j.cnki.1007-3639.2020.05.007.

摘要

背景与目的：免疫检查点抑制剂（immune checkpoint inhibitor，ICI）已成为肿瘤治疗的重要手段，然而伴随其显著疗效的是药物相关不良反应。观察帕博丽珠单抗在晚期黑色素瘤治疗中的安全性；初步探讨程序性死亡［蛋白］-1（programmed death-1，PD-1）单抗不良事件发生的预测因子及与疗效的相关性。方法：收集2016年8月—2017年7月期间在北京大学肿瘤医院入组一项“帕博丽珠单抗作为二线治疗中国局部晚期或转移性黑色素瘤的Ⅰb期临床研究（Keynote-151）”的54例患者的临床资料，包括性别、年龄、疾病分期、原发部位、既往化疗史、美国东部肿瘤协作组（Eastern Cooperative Oncology Group，ECOG）评分及基线外周血细胞计数，以及药物治疗相关不良事件和疗效相关信息。不良事件根据通用不良事件术语标准（Common Terminology Criteria Adverse Events，CTCAE）4.03版评价，疗效根据实体肿瘤疗效评价标准（Response Evaluation Criteria in Solid Tumors，RECIST）1.1标准评估。结果：帕博丽珠单抗在晚期黑色素瘤治疗中不良事件发生率达88.9%（48/54），严重不良事件发生率为13.0%（7/54），无死亡病例；肝毒性是导致中断和终止用药的主要原因；分析严重不良事件的发生与所观察各项临床特征及实验室检查指标之间均无显著相关性；不良事件的发生与疗效相关分析提示白癜风（P=0.001）和甲状腺功能异常（P=0.007）与疗效相关。结论：帕博丽珠单抗治疗晚期黑色素瘤不良反应发生率较高，但以1~2级为主，耐受性较好；肝毒性对试验药物应用影响最大；白癜风和甲状腺功能异常均可能是疗效较好的预测因子。

Abstract

Background and purpose: Immune checkpoint inhibitor (ICI) has become an important means of tumor treatment. However

their significant effects are accompanied by drug-related adverse reactions. This study aimed to observe the safety of pembrolizumab in patients with advanced melanoma

and to explore the clinical predictive factors for adverse events risk and the correlation between adverse events and responses with anti-programmed death-1 (PD-1) monoclonal antibodies. Methods: The clinical data of 54 patients who were enrolled in a phase Ⅰb study of pembrolizumab as a second-line treatment for Chinese patients with advanced or metastatic melanoma (KEYNOTE-151) were collected at the Peking University Cancer Hospital from Aug. 2016 to Jul. 2017. Clinical information included gender

age

metastatic stage

primary site

previous chemotherapy history

Eastern Cooperative Oncology Group (ECOG) score

blood laboratory tests

adverse events and treatment outcome. The occurrence of adverse events was analyzed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grading scale. The response was calculated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results: The rate of adverse events was 88.9% (48/54) in patients with advanced melanoma treated with pembrolizumab

and the rate of serious adverse events was 13.0% (7/54). There was no death. Hepatotoxicity was the main cause of interruption and discontinuation of medication. We failed to show an association between both of the clinical features and blood cell count and occurrence of serious adverse events

while vitiligo (P=0.001) and thyroid dysfunction (P=0.007) were significantly associated with better response. Conclusion: Although pembrolizumab has a higher incidence of adverse reactions in advanced melanoma

they are generally grade 1-2 with better tolerance. Hepatotoxicity has the most significant effect on the study drug. Vitiligo and thyroid dysfunction may both be predictive factors of better efficacy in patients receiving PD-1 monoclonal antibodies.

关键词

Keywords

references

浏览量

2698

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

暂无数据